Ramloid

Package leaflet: Information for the user

Ramloid hard capsules 5 mg/5 mg/12.5 mg, hard capsules 5 mg/5 mg/25 mg, hard capsules 10 mg/5 mg/25 mg, hard capsules 10 mg/10 mg/25 mg

Ramipril/amlodipine/hydrochlorothiazide
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Ramloid is and what it is used for
2. What you need to know before taking Ramloid
3. How to take Ramloid
4. Possible side effects
5. How to store Ramloid
6. Contents of the pack and other information

1. What Ramloid is and what it is used for

Ramloid contains three active substances called ramipril, amlodipine, and hydrochlorothiazide.
Ramipril belongs to a group of medicines known as ACE inhibitors (angiotensin-converting enzyme inhibitors). This medicine works by:

• Reducing the body's production of substances that may increase blood pressure
• Relaxing and widening blood vessels
• Making it easier for the heart to pump blood throughout the body

Amlodipine belongs to a group of medicines called calcium antagonists. This medicine works by:

• Relaxing blood vessels, allowing blood to flow more easily

Hydrochlorothiazide belongs to a group of medicines known as "thiazide diuretics" or "water tablets".
This medicine works by:

• Increasing the production of water (urine). This helps to lower blood pressure.

Ramloid can be used to treat high blood pressure (hypertension) in adult patients who are adequately controlled with the individual components given at the same doses as in the combination, but as separate tablets.

2. What you need to know before taking Ramloid

Do not take Ramloid

• If you are allergic to ramipril, amlodipine or hydrochlorothiazide (active substances), to any other calcium antagonist or ACE inhibitor, or to any sulfonamide-derived medicine, or to any of the other ingredients of this medicine (listed in section 6).
• If you have severe narrowing of the aortic heart valve (aortic stenosis) or cardiogenic shock (a condition in which the heart is unable to supply sufficient blood to the body).
• If you have previously had a severe allergic reaction called "angioedema". Signs include itching, hives, red spots on the hands, feet and throat, swelling of the throat and tongue, swelling around the eyes and lips, difficulty breathing and swallowing.
• If you are undergoing dialysis or any other type of blood filtration. Depending on the equipment used, treatment with Ramloid may not be suitable for you.
• If you have severe kidney problems.
• If you suffer from liver failure.
• If you have abnormal levels of salts (calcium, potassium, sodium) in your blood.
• If you have kidney problems in which blood supply to the kidneys is reduced (renal artery stenosis).
• During the last 6 months of pregnancy (see section “Pregnancy and breastfeeding” below).
• If you have excessively low or unstable blood pressure.
• If you have heart failure following a heart attack.
• If you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.

Do not take Ramloid if you fall into any of the conditions described above. If you have any doubts, consult your doctor before taking Ramloid.
Warnings and precautions

• If you are elderly and your dose needs to be increased;
• If you have heart, liver or kidney problems;
• If you suffer from severe increases in blood pressure (hypertensive crisis);
• If you have lost significant amounts of body salts or fluids (due to vomiting, diarrhoea, excessive sweating, low-salt diet, prolonged use of diuretics [water tablets] or dialysis);
• If you are breastfeeding;
• If you are due to undergo treatment to reduce allergy to bee or wasp stings (desensitisation therapy);
• If you are about to receive an anaesthetic that may be administered during surgery or dental procedures. In this case, you may need to stop treatment with Ramloid one day before the procedure; consult your doctor;
• If you have high levels of potassium in the blood (as shown by blood tests);
• If you are taking medicines or have medical conditions that could reduce the amount of sodium in your blood. Your doctor may prescribe regular blood tests, particularly to monitor blood sodium levels, especially if you are elderly;
• If you are taking medicines called mTOR inhibitors (e.g., temsirolimus, everolimus, sirolimus), vildagliptin or racecadotril, as they may increase the risk of angioedema, a serious allergic reaction;
• If you have a vascular collagen disease such as scleroderma or systemic lupus erythematosus;
• If you experience decreased vision or eye pain, particularly if you are at risk of developing a condition called glaucoma or if you are allergic to penicillin or sulphonamide drugs;
• If you develop photosensitivity reactions, you must stop treatment with Ramloid;
• If you have diabetes, your insulin dosage may need to be adjusted or you may need to use antidiabetic medicines;
• If you are taking any of the following medicines used to treat high blood pressure: or an angiotensin II receptor blocker (ARB), also known as a sartan (e.g. valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes; or aliskiren;
• If you have had skin cancer or if you suddenly develop a skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of skin and lip cancer (non-melanoma skin cancer). During treatment with Ramloid, protect your skin from exposure to sunlight and UV rays.
  Your doctor may check your kidney function, blood pressure and levels of electrolytes (e.g., potassium) in your blood at regular intervals. See also the information under the section “Do not take Ramloid”.
  Inform your doctor if you think you are (or might become) pregnant. The use of Ramloid is not recommended during the first 3 months of pregnancy and may cause serious harm to the baby after the first trimester of pregnancy (see the section “Pregnancy and breastfeeding” below).

Children and adolescents
The use of Ramloid is not recommended in children and adolescents under 18 years of age due to lack of data on safety and efficacy.

Other medicines and Ramloid
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines not requiring a prescription (including herbal medicines). Ramloid may affect how some other medicines work.
In addition, some medicines may affect how Ramloid works.
Your doctor may need to adjust your dose and/or take other precautions:

• If you are taking an angiotensin II receptor blocker (ARB) or aliskiren (see also the information under “Do not take Ramloid” and “Warnings and precautions”).

The following medicines may negatively affect the effectiveness of Ramloid:

• Medicines used to relieve pain and inflammation (e.g., non-steroidal anti-inflammatory drugs [NSAIDs] such as ibuprofen or indomethacin and acetylsalicylic acid)
• Medicines used to treat low blood pressure, shock, heart failure, asthma or allergies such as ephedrine, noradrenaline or adrenaline. Your doctor should monitor your blood pressure.
• Rifampicin (an antibiotic used to treat tuberculosis)
• Hypericum perforatum (St. John’s wort, a herbal medicine used for depression)

The following medicines may increase the likelihood of side effects when taken together with Ramloid:

• Medicines used to relieve pain and inflammation (e.g., non-steroidal anti-inflammatory drugs [NSAIDs] such as ibuprofen or indomethacin and acetylsalicylic acid);
• Medicines for cancer (chemotherapy);
• Medicines to prevent organ rejection after transplantation, such as cyclosporine;
• Medicines that may lower potassium levels in the blood. These include medicines for constipation, glucocorticoids, tetracosactide, amphotericin B (used for fungal infections) and ACTH (used to assess adrenal gland function);
• Diuretics (water tablets) such as furosemide;
• Desmopressin;
• Steroids used to treat inflammation, such as prednisolone;
• Medicines that may increase potassium levels in the blood such as spironolactone, triamterene, amiloride, potassium salts, trimethoprim alone or in combination with sulfamethoxazole (for bacterial infections) and heparin (to thin the blood);
• Medicines for heart problems, including heart rhythm disorders:
• Calcium supplements;
• Allopurinol (used to lower uric acid levels in the blood);
• Procainamide (for heart rhythm disorders);
• Cholestyramine (to reduce blood fat levels);
• Carbamazepine, oxcarbazepine (for epilepsy);
• Ketoconazole, itraconazole (to treat fungal infections);
• Erythromycin, clarithromycin (antibiotics used to treat certain bacterial infections);
• Ritonavir, indinavir, nelfinavir (so-called protease inhibitors used to treat HIV infection);
• Verapamil, diltiazem (to treat certain heart diseases and high blood pressure);
• Dantrolene (administered by infusion in cases of severe body temperature disturbances);
• Temsirolimus (for cancer);
• Sirolimus, everolimus (to prevent transplant rejection);
• Vildagliptin (to treat type 2 diabetes);
• Racecadotril (used for diarrhoea);
• Tacrolimus (used to control the immune response; allows the body to accept a transplanted organ);
• Other medicines to lower blood pressure, such as phosphodiesterase type 5 inhibitors (for erectile dysfunction), nitrates, alpha-blockers (used in urology to reduce tension in smooth muscles of the prostate and urethra), tricyclic antidepressants and neuroleptics;
• Medicines that affect gastrointestinal motility, i.e., anticholinergic agents.

The following medicines may be affected by Ramloid:

• Medicines for diabetes, such as oral antidiabetics and insulin. Ramloid may lower blood sugar levels. Monitor your blood sugar levels carefully while taking Ramloid;
• Lithium (for psychiatric conditions): Ramloid may increase lithium levels in the blood. Your doctor must monitor your blood lithium levels;
• Simvastatin (a medicine to lower cholesterol): amlodipine increases exposure to simvastatin. Your doctor should reduce the dose of simvastatin if you are taking Ramloid;
• Quinine (for malaria);
• Medicines containing iodine; these may be used during CT scans or X-rays in hospital;
• Penicillin (for infections);
• Oral medicines to thin the blood (oral anticoagulants), such as warfarin.

If any of the above conditions apply to you (or if you have any doubts), consult your doctor before taking Ramloid.
Check with your doctor or pharmacist before taking this medicine:

• If you are undergoing a test for parathyroid function. The combination ramipril/hydrochlorothiazide may alter the results of this test.
• If you are an athlete and are subject to anti-doping controls. The combination ramipril/hydrochlorothiazide may cause a positive anti-doping test.

Ramloid with food, drinks and alcohol

• Ramloid can be taken before and after meals.
• People taking Ramloid must not eat grapefruit or drink grapefruit juice. Grapefruit and grapefruit juice may cause increased levels of the active ingredient amlodipine in the blood, resulting in an unexpected and potentially dangerous increase in the blood pressure-lowering effect of Ramloid.
• Drinking alcohol during treatment with Ramloid may cause dizziness or drowsiness. If you have any doubts about how much alcohol is safe during treatment with Ramloid, discuss this with your doctor, as medicines used to lower blood pressure and alcohol may enhance each other's sedative effects.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Inform your doctor if you think you are (or might become) pregnant. Ramloid should not be taken during the first 12 weeks of pregnancy and none of its components should be taken after week 13, as use of these medicines during pregnancy may harm the unborn baby. If you become pregnant while taking Ramloid, inform your doctor immediately.
If you plan to become pregnant, you should consider switching to an appropriate alternative treatment.

Breastfeeding
Do not take Ramloid if you are breastfeeding. Consult your doctor or pharmacist before taking any medicine.

Fertility
There are insufficient data on the potential effect on fertility.

Driving and using machines
Ramloid may affect your ability to drive vehicles or operate machinery. If this medicine causes nausea, dizziness, tiredness or headache, avoid driving or operating machinery and contact your doctor immediately.

3. How to take Ramloid

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The recommended dose is 1 capsule daily, at the strength prescribed by your doctor.
Depending on the effect of the medicine, your doctor may adjust the dose.
The maximum dose is 1 capsule once daily of the 10 mg/10 mg/25 mg strength.
Take this medicine by mouth at the same time each day, either before or after meals.
Swallow the hard capsule whole with liquid.
Avoid crushing or chewing the hard capsules.
Do not take Ramloid with grapefruit juice.

Liver and kidney diseases
Dosage may be adjusted in the presence of liver or kidney diseases.

Elderly
Your doctor may reduce the initial dose and adjust treatment more gradually.
Administration of Ramloid capsules is not recommended in very elderly and frail patients.

Use in children and adolescents
The use of Ramloid is not recommended in children and adolescents under 18 years of age due to lack of safety and efficacy data.

If you take more Ramloid than you should
Taking too many capsules may cause a drop in blood pressure, lowering it to dangerous levels. You may experience dizziness, lightheadedness, fainting, or weakness. If the drop in blood pressure is severe enough, shock may occur. Your skin may become cold and clammy, and you may lose consciousness. If you have taken an excessive amount of Ramloid, seek immediate medical attention. Do not drive yourself to the hospital; have someone drive you or call an ambulance. Take the medicine package with you; this way, the doctor will know what you have taken.

If you forget to take Ramloid
If you forget to take a capsule, skip the missed dose completely and take the next dose at your usual time. Do not take a double dose to make up for the missed dose.

If you stop taking Ramloid
Your doctor will tell you how long you should take this medicine. If you stop treatment prematurely, your condition may return.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Stop taking Ramloid and consult a doctor immediately if you experience
any of the following serious side effects (in such cases you may require urgent medical treatment):

• Swelling of the face, lips, or throat causing difficulty in swallowing or breathing, accompanied by itching and skin rash. These could be signs of a severe allergic reaction to Ramloid.
• Severe skin reactions including skin rash, mouth ulcers, worsening of a pre-existing skin condition, redness, blistering or peeling of the skin (such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or erythema multiforme).

Contact your doctor immediately if you experience:

• Rapid or irregular heartbeat (palpitations), chest pain, tightness in the chest, or more serious problems such as heart attack or stroke.
• Shortness of breath or cough. These could be signs of lung problems, such as inflammation.
• Increased tendency to bruise, bleeding that lasts longer than usual, any sign of bleeding (e.g., bleeding gums), appearance of purple spots on the skin, or increased susceptibility to infections, sore throat and fever, fatigue, feeling faint, dizziness or paleness. These may be signs of blood or bone marrow problems.
• Severe stomach pain that may radiate to the back. These could be signs of inflammation of the pancreas (pancreatitis).
• Fever, chills, fatigue, loss of appetite, stomach pain, nausea, yellowing of the skin or eyes (jaundice). These may be signs of liver problems such as inflammation (hepatitis) or liver damage.

Other side effects include:
Inform your doctor if any of the conditions listed below worsen or persist for more than a few days.
Very common: may affect more than 1 in 10 people

• Swelling (edema)
• Hypokalemia
• Hyperlipidemia

Common: may affect up to 1 in 10 people

• Headache, dizziness, drowsiness associated with sleepiness (especially at the beginning of treatment), feeling of fatigue (tiredness)
• Awareness of heartbeat (palpitations)
• Swelling of the ankles
• Low blood pressure (hypotension), especially when standing up or sitting down quickly (orthostatic hypotension), fainting (syncope), hot flushes
• Dry, persistent cough, inflammation of the sinuses (sinusitis), bronchitis, shortness of breath (dyspnea)
• Abdominal pain, diarrhea, gastrointestinal inflammation, digestive disturbances and abdominal discomfort (including indigestion), nausea, vomiting, changes in bowel habits (including diarrhea and constipation), loss of appetite (anorexia), spasms
• Skin rash with or without blistering, hives
• Chest pain
• Muscle cramps or pain (myalgia)
• Blood tests showing lower than normal levels of magnesium and sodium
• Feeling of weakness and exhaustion (asthenia)
• Blood tests showing reduced platelet count (thrombocytopenia)
• Blood tests showing increased levels of uric acid or potassium
• Inability to achieve an erection (impotence)
• Vision disturbances (including blurred vision and double vision)

Uncommon: may affect up to 1 in 100 people

• Swelling of the skin, mucous membranes, and surrounding tissues (angioedema/Quincke's edema; in extremely rare cases, airway obstruction due to angioedema may be fatal)
• Swelling of arms and legs (peripheral edema; this could be a sign of fluid retention)
• Swelling of the intestine (angioedema of the small intestine)
• Mood changes, depression, anxiety, nervousness, restlessness, sleep disturbances (insomnia)
• Ringing in the ears (tinnitus)
• Sneezing/runny nose (rhinitis), stuffy nose
• Difficulty breathing (bronchospasm), including worsening of asthma
• Dry mouth, upper abdominal pain, including gastritis
• Inflammation of the pancreas (pancreatitis; fatal cases have been reported very rarely with ACE inhibitors)
• Kidney impairment including kidney failure, urinary disorders, need to urinate more frequently during the day, increased need to urinate at night (nocturia)
• Worsening of pre-existing proteinuria (abnormally high levels of protein in urine)
• Feeling unwell
• Weight gain or weight loss
• Dizziness, tremor
• Hair loss (alopecia)
• Itching, presence of small bleeding spots or bleeding areas on the skin (purpura), skin color changes, rash
• Unusual skin sensations such as numbness, tingling, pricking, burning, or crawling sensations (paresthesia), reduced skin sensitivity (hypoesthesia)
• Loss (ageusia) or alteration (dysgeusia) of taste
• Excessive sweating (hyperhidrosis)
• Heart attack (myocardial infarction), heart vessel disease (myocardial ischemia), chest tightness and pain (angina pectoris), increased (tachycardia) or irregular (arrhythmia) heartbeat
• Slowed heartbeat (bradycardia), specific heart rhythm disorders (atrial fibrillation, ventricular tachycardia)
• Joint pain (arthralgia), back pain, generalized pain
• Increased body temperature/fever (pyrexia)
• Reduced sexual desire in men or women, breast enlargement in males (gynecomastia)
• Increased number of certain white blood cells (eosinophilia) detected during blood tests
• Blood tests showing changes in liver function (increased liver enzymes and/or conjugated bilirubin), pancreatic function (increased pancreatic enzymes), or kidney function (increased creatinine)
• Cough
• Necrotizing vasculitis (vasculitis, cutaneous vasculitis)

Rare: may affect up to 1 in 1,000 people

• Feeling or state of confusion, balance disorders
• Redness and swelling of the tongue (glossitis)
• Inflammation and peeling of the skin (exfoliative dermatitis)
• Nail problems, e.g., loss or separation of a nail from its bed (onycholysis)
• Redness, itching, swelling, or tearing of the eyes (conjunctivitis)
• Hearing disturbances
• Yellowing of the skin (cholestatic jaundice), hepatocellular damage
• Narrowing of blood vessels (vascular stenosis)
• Blood circulation disorders (hypoperfusion)
• Inflammation of blood vessels (vasculitis)
• Blood tests showing reduced numbers of red blood cells, white blood cells (including neutropenia or agranulocytosis, leukopenia), or hemoglobin levels
• Blood tests showing higher than normal sugar levels. If you have diabetes, this may worsen your condition
• Sensitivity to sunlight or other light sources (photosensitivity)
• Hypercalcemia
• Hypersensitivity reaction

Very rare: may affect up to 1 in 10,000 people

• Widespread skin rash with blistering and peeling of the skin, particularly around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome)
• Inflammation of the liver (hepatitis, mostly cholestatic)
• Skin rash that may blister and appear as small targets (dark central spots surrounded by a lighter area, with a dark ring around the edge) (erythema multiforme)
• Lupus erythematosus-type reaction, reactivation of lupus erythematosus, necrotizing vasculitis, and toxic epidermal necrolysis
• Enlargement of gum tissue (gingival hyperplasia)
• Increased muscle tone (hypertonia)
• Peripheral nervous system disorder (peripheral neuropathy)
• Bone marrow failure
• Blood tests showing excessive numbers of damaged red blood cells (hemolytic anemia)
• Allergic reactions
• Hypochloremic alkalosis
• Respiratory distress (including pneumonia and pulmonary edema)

Not known: (frequency cannot be estimated from available data)
Inform your doctor if any of the conditions listed below worsen or persist for more than a few days.

• Blood tests showing severely reduced numbers of red blood cells, white blood cells, and platelets (pancytopenia)
• Anaphylactic or anaphylactoid reactions
• Blister formation on the skin (pemphigus)
• Increased levels of antinuclear antibodies
• Attention disorders
• Inflammation of the oral mucosa with small ulcers (aphthous stomatitis)
• Aplastic anemia
• Changes in the color of fingers and toes when cold, followed by tingling or pain upon warming (Raynaud's phenomenon)
• Cerebral ischemia, including ischemic stroke and transient ischemic attack
• Impairment of psychomotor skills
• Burning sensation
• Changes in smell (parosmia)
• Acute liver failure, cytolytic and cholestatic hepatitis (with fatal outcomes in extremely rare cases)
• Skin inflammation (psoriasiform dermatitis), severe skin rashes (bullous pemphigoid or lichenoid eruption), worsening of skin peeling or cracking (worsening of psoriasis), mucosal redness (enantema)
• Concentrated urine (dark-colored), feeling unwell, muscle cramps, confusion, and seizures which could be due to inappropriate ADH (antidiuretic hormone) secretion. If you experience these symptoms, contact your doctor as soon as possible.
• Tremor, rigid posture, expressionless face, slowness of movement, shuffling gait with balance problems
• Acute angle-closure glaucoma
• Skin and lip tumors (non-melanoma skin cancers)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your <,>. You can also report side effects directly via the national reporting system at the website:
http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ramloid

Store below 30 °C.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after EXP. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Ramloid contains
Ramloid 5 mg/5 mg/12.5 mg hard capsules:
one capsule contains 5 mg ramipril, 5 mg amlodipine (as amlodipine besilate), 12.5 mg hydrochlorothiazide.
Ramloid 5 mg/5 mg/25 mg hard capsules:
one capsule contains 5 mg ramipril, 5 mg amlodipine (as amlodipine besilate), 25 mg hydrochlorothiazide.
Ramloid 10 mg/5 mg/25 mg hard capsules:
one capsule contains 10 mg ramipril, 5 mg amlodipine (as amlodipine besilate), 25 mg hydrochlorothiazide.
Ramloid 10 mg/10 mg/25 mg hard capsules:
one capsule contains 10 mg ramipril, 10 mg amlodipine (as amlodipine besilate), 25 mg hydrochlorothiazide.

The other components are:
Capsule contents: microcrystalline cellulose, anhydrous calcium hydrogen phosphate, pregelatinized maize starch, sodium starch glycolate (type A), sodium stearyl fumarate
Capsule shell (5 mg/5 mg/12.5 mg): red iron oxide (E172), black iron oxide (E172), titanium dioxide (E171), gelatin
Capsule shell (5 mg/5 mg/25 mg): red iron oxide (E172), yellow iron oxide (E172), titanium dioxide (E171), gelatin
Capsule shell (10 mg/5 mg/25 mg): red iron oxide (E172), yellow iron oxide (E172), titanium dioxide (E171), gelatin
Capsule shell (10 mg/10 mg/25 mg): red iron oxide (E172), yellow iron oxide (E172), black iron oxide (E172), titanium dioxide (E171), gelatin

Ramloid hard capsules 5 mg/5 mg/12.5 mg:
capsule with an opaque pink cap and an opaque light grey body
Ramloid hard capsules 5 mg/5 mg/25 mg:
capsule with an opaque pink cap and an opaque ivory body
Ramloid hard capsules 10 mg/5 mg/25 mg:
capsule with an opaque dark pink cap and an opaque yellow body
Ramloid hard capsules 10 mg/10 mg/25 mg:
capsule with an opaque brown cap and an opaque caramel body
Pack sizes of 10, 28, 30, 60, or 100 hard capsules in blisters contained in a cardboard box.
Not all pack sizes may be marketed.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Adamed S.r.l.,
Via G. Mazzini 20
20123 Milan
Italy
Manufacturers:
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
Poland